Cystinosis: A genetic disease characterized by the widespread deposition of the amino acid cystine in cells due to a defect in cystine transport. (Cystine normally forms after protein degradation and is transported from structures called lysosomes into the cytoplasm. In cystinosis, cystine accumulates in the lysoosmes and eventually forms crystals throughout the body. Cystinosis is therefore a lysosomal storage disease.)
The disease is inherited in an autosomal recessive manner. The gene that is mutated in the disease is symbolized CTNS and has been mapped to chromosome 17 (to region 17p13.1). It encodes the protein cystinosin which transports cystine.
The initial symptoms of cystinosis are renal and appear between 6 and 12 months of age. The accumulation of cystine results in what is called the renal Fanconi syndrome, a failure of the tubules in the kidney to reabsorb small molecules, causing increased urinary loss of electrolytes (sodium, potassium, bicarbonate), minerals, glucose, amino acids, and water. These losses results in polyuria (excessive urination), polydipsia (excessive intake of fluid), dehydration (from the excess urination) hypophosphatemic rickets (due to loss of phosphate in the urine), and growth retardation (due to the renal disease). Photophobia (excess sensitivity of the eye to light) occurs between mid-childhood and adolescence due to accumulation of cystine crystals in the cornea. Cystine storage in the thyroid leads to hypothyroidism usually around age 10. Intelligence remains normal.
Treatment of the renal Fanconi syndrome is by replacing the renal losses and supplementing with citrate to alkalinize the blood. Phosphate replacement prevents and heals the rickets. Vitamin D helps the intestinal absorption of phosphate. The outlook with this disease changed for the better with cystine depletion therapy using cysteamine (Cystagon) which depletes cystinuric cells of most of their cystine, prevents kidney failure, and enhances growth.
This is the classic nephropathic type of cystinosis. There are two other types of cystinosis. One is intermediate cystinosis, which has the same features as the nephropathic type but is much slower in its progression. The other type is ocular cystinosis, which has the typical eye findings but no systemic disease.